Pharmacological analysis of intrinsic neuronal oscillations in rd10 retina.
Pharmacological analysis of intrinsic neuronal oscillations in rd10 retina.
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DOI：
10.1371/journal.pone.0099075
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Müller F
中科院分区：
文献类型：
--
作者：
Biswas S;Haselier C;Mataruga A;Thumann G;Walter P;Müller F
在广泛使用的视网膜变性小鼠模型 rd1 中，光感受器的丧失导致剩余视网膜网络中出现约 10-16 Hz 的节律性电活动。最近的研究表明，这种振荡是在所有无长突细胞和 ON-双极细胞的电耦合网络内形成的。第二种小鼠模型 rd10 显示出退化的延迟发作和较慢的进展，使该小鼠品系成为人类视网膜色素变性的更好模型。在 rd10 中，振荡发生的频率为 3-7 Hz，这引发了两个小鼠模型中振荡是否具有相同起源的问题。随着 rd10 越来越多地被用作开发实验疗法的模型，了解自发节律活动背后的机制非常重要。为了研究 rd10 视网膜振荡的特性，我们将多电极记录与视网膜网络的药理学操作结合起来。离子型谷氨酸受体和间隙连接的阻断剂消除了振荡。振荡的频率和幅度受到抑制性受体阻滞剂的强烈调节，并且在较小程度上受到 HCN 通道阻滞剂的调节。总之，虽然我们发现 rd10 与 rd1 的节律活性药理学调节存在一定差异，但总体模式看起来相似。这表明节律性活动的产生可能是 rd1 和 rd10 视网膜中类似机制的基础。
In the widely used mouse model of retinal degeneration, rd1, the loss of photoreceptors leads to rhythmic electrical activity of around 10–16 Hz in the remaining retinal network. Recent studies suggest that this oscillation is formed within the electrically coupled network of AII amacrine cells and ON-bipolar cells. A second mouse model, rd10, displays a delayed onset and slower progression of degeneration, making this mouse strain a better model for human retinitis pigmentosa. In rd10, oscillations occur at a frequency of 3–7 Hz, raising the question whether oscillations have the same origin in the two mouse models. As rd10 is increasingly being used as a model to develop experimental therapies, it is important to understand the mechanisms underlying the spontaneous rhythmic activity. To study the properties of oscillations in rd10 retina we combined multi electrode recordings with pharmacological manipulation of the retinal network. Oscillations were abolished by blockers for ionotropic glutamate receptors and gap junctions. Frequency and amplitude of oscillations were modulated strongly by blockers of inhibitory receptors and to a lesser extent by blockers of HCN channels. In summary, although we found certain differences in the pharmacological modulation of rhythmic activity in rd10 compared to rd1, the overall pattern looked similar. This suggests that the generation of rhythmic activity may underlie similar mechanisms in rd1 and rd10 retina.
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